Biologics Before Chemotherapy: Treatment Updates for Mycosis Fungoides, Sézary Syndrome

The use of chemotherapy to treat mycosis fungoides and Sézary syndrome, the most common forms of cutaneous T-cell lymphomas, led to a shorter time to next treatment compared with the use of alpha interferon and histone deacetylase inhibitors (HDACi), results of a new study indicated.

Based on these results, study researcher Miles Prince, MD, of Peter MacCallum Cancer Centre, Australia, said that chemotherapy should be avoided and reserved until other treatment options, such as interferon, bexarotene, HDACi, or – in the case of Sézary syndrome – extracorporeal photophoresis (ECP), have been used. “Interferon should be considered as a standard front-line therapy in patients able to tolerate it,” Dr. Prince told ASH Clinical News. 

Despite the increasing number of systemic therapies being examined and available for the treatment of mycosis fungoides and Sézary syndrome, to date, there have been no comparative studies of systemic therapies.

According to Dr. Prince, the physicians who treat these conditions recognize that chemotherapy has poor outcomes, but there are no solid data to examine how this compares with more traditional treatments (such as interferon) and newer therapies (such as HDACi).

Dr. Prince and researchers conducted a retrospective analysis of 198 patients with mycosis fungoides and Sézary syndrome undergoing systemic therapies – 53 percent of whom had advanced-stage disease. The researchers followed patients for a median of 4.9 years, during which time 37.9 percent of the patients died. Median survival was 11.4 years.

Twenty-eight treatment modalities were analyzed, with patients receiving a median of three lines of therapy.

In patients with advanced disease, low-dose methotrexate was the most common first-line therapy; in patients with early-stage disease, psoralen plus ultraviolet A radiation (PUVA) was the most common first-line therapy. Overall, the median time to next treatment (TTNT; the study’s primary endpoint) was 5.4 months for all treatments analyzed together (95% CI 5.1- 6.1). For a breakdown of the TTNT analysis, see the TABLE.

When compared with chemotherapy, alpha interferon was associated with a significantly longer TTNT (p<.0.0001) – a benefit that was consistent in patients with early and advanced disease and patients with mycosis fungoides and Sézary syndrome. HDACi and biologic agents (denileukin diftitox, bexarotene, and alemtuzumab) also provided significantly greater TTNT overall, compared with chemotherapy. The superiority of HDACi, the authors noted, was only in patients with advanced disease and when used as second-, third-, or fourth-line therapy.

“Our analysis highlights the inability of chemotherapy to provide durable disease control,” Dr. Prince and colleagues concluded. “Chemotherapy was most efficacious when used as first-line therapy, but efficacy quickly declined when used as mid- or late-line therapy — non–first-line being where the majority of patients in this study underwent chemotherapy.”

Dr. Prince noted that in certain circumstances, such as transformed disease, there may still be a role for chemotherapy early in therapy, but that this needs further study.


    Hughes CFM, Khot A, McCormack C, et al. Lack of durable disease control with chemotherapy for mycosis fundgoides and Sézary syndrome: a comparative study of systemic therapy. Blood. 2014 October 21. [Epub ahead of print]
TABLE. Time to Next Treatment Analysis
Median TNTT (months; 95% CI)
PUVA 36.3 (9.5 – 47.9)
Allogeneic hematopoietic stem cell transplant (AlloSCT) 7.8 (11.5 – N/A)
Alpha interferon 8.7 (6.0 – 18.0)
Single- or multi-agent chemotherapy 3.9 (3.2 – 5.1)
Low-dose methotrexate 5.0 (3.6 – 6.5)
HDACi 4.5 (4.0 – 6.1)
Bexarotene 7.3 (2.6 – 110.8)
Alemtuzumab 4.1 (2.7 – 6.5)
Denileukin diftitox 5.1 (2.7 – 6.5)
Autologous hematopoietic stem cell transplant (AuSCT) 7.8 (4.7 – 24.4)
ECP 9.2 (5.9 – 12.8)
Total skin electron beam radiation (TSEB) 7.8 (4.4 – 14.7)